Prostaglandin 2 biosynthesis and
Prostaglandin biosynthesis starts with arachidonic acid
that is oxidized to Prostaglandin H2 (PGH2) by Prostaglandin
G/H synthase 1 precursor (COX-1 (PTGS1)) or by Prostaglandin
G/H synthase 2 precursor (COX-2 (PTGS2)) , , , , . An alternative
reaction involves oxidation of arachidonic acid resulting in
formation of Prostaglandin G2 (PGG2) catalyzed either by
COX-1 (PTGS1) ,  and
COX-2 (PTGS2) , , or by
Epidermis-type lipoxygenase 3 (LOXE3) ,  and Arachidonate 12-lipoxygenase, 12R type
(ALOX12B) , .
COX-1 (PTGS1) and COX-2 (PTGS2)
, ,  can oxidize
PGH2 directly to PGG2, whereas
PGG2 can be reduced directly to
PGH2 by a number of enzymes, e.g., Peroxiredoxin-1
(PRDX2), Thioredoxin-dependent peroxide reductase,
mitochondrial precursor (PRDX3), Peroxiredoxin-4
(PRDX4) , Peroxiredoxin-5, mitochondrial
precursor (PRDX5) , ). This
reduction is coupled with the oxidation of reduced
PGH2 can be directly transformed to Prostaglandin E2
(PGE2) by the Prostaglandin E synthase
(PGES) ,  and Prostaglandin
E synthase 2 (PGES2) , , , and to Prostaglandin D2 (PGD2) by the
Alcohol dehydrogenase [NADP+] (ALDX) .
PGD2 can also be formed by Aldo-keto reductase family 1
member C3 (AKR1C3) with
11-epi-PGF2alpha as a precursor , .
There are various ways to form Prostaglandin F2 alpha (PGF2
alpha). One way is by reduction of the PGE2
catalyzed by Carbonyl reductase [NADPH] 1 (CBR1) , , Carbonyl reductase [NADPH] 2
(CBR2) , ,
Carbonyl reductase [NADPH] 3  and
Dehydrogenase/reductase SDR family member 4 (DHRS4) , . PGF2 alpha can also be
synthesized from PGD2 in the reaction catalyzed by
ALDX and AKR1C3 , . Another way involves transformation of PGH2
also catalyzed by AKR1C3 .
PGE2 can also be reduced to
15-oxo-PGE2 either by 15-hydroxyprostaglandin dehydrogenase
[NAD+] (HPGD) ,  or
CBR1. The latter subsequently catalyzes the reduction of
15-oxo-PGE2 to 15-ketoprostaglandin F2 alpha
(15-Keto-PGF2alpha) that is in turn reduced by
CBR1 to PGF2 alpha.
PGE2 loses water moiety and transforms to Prostaglandin
A2 (PGA2). The latter is further transformed to
Prostaglandin C2 (PGC2). PGC2
can be also transformed to Prostaglandin B2 (PGB2) . PGD2 can be transformed to Prostaglandin J2
(PGJ2). Prostaglandin I2 (prostacyclin) synthase
(PTGIS) catalyzes dehydration on
PGH2 resulting in the formation of Prostaglandin I2
PGH2 is metabolized by a set of enzymes. Thromboxane A
synthase 1 (platelet) (THAS) forms
12-hydroxyheptadeca-5,8,10-trienoic acid and
malonic dialdehyde as a byproduct, Thromboxane
A(,2) ,  and Thromboxane
B2. Thromboxane A2 in its turn can
spontaneously convert to Thromboxane B2. Prostaglandin E
synthase (PGES) and Prostaglandin E synthase 2
(PGES2) catalyze the transformation of
PGH2 to 15-hydroperoxy-PGE1 , , . Cytochrome P450, family 4, subfamily F, polypeptide
(CYP4F12) reduces PGH2 to
20-hydroxy-prostaglandin H1 , . This enzyme also catalyzes the reduction of PGE2
to 9-oxo-PGF2alpha. PGE2 can be
transformed to 5,6-dihydro-15-keto-prostaglandin E2 by
HPGD , .
PGE2 metabolite 15-oxo-PGE2
is reduced to 13,14-dihydro-15-keto-PGE2 by Prostaglandin
reductase 1 (LTB4DH), while another metabolite
15-keto-PGF2alpha is also reduced by the same enzyme to
13,14-dihydro-15-keto-PGF2alpha. The latter product is
subsequently transformed by CBR1 to
13,14-dihydro-PGF2alpha. 15-Keto-PGF2 alpha
can also be formed from PGF2 alpha via the
reaction catalyzed by CBR1  or
HPGD , .
PGJ2 is metabolically transformed to
THAS catalyzes the transformation of
15-hydroperoxy-5,8,10-heptadecatrienoic acid with
Malonic dialdehyde as a byproduct, or to
PGES and PGES2 transform
PGG2 to 15-hydroperoxy-PGE2
, . Prostaglandin D2 synthase (brain)
(PGHD) and Prostaglandin D2 synthase 2 hematopoietic
(PGDS) can also catalyze formation of
15-hydroperoxy-PGD2 , , . PTGIS hydroxylates
PGI2 also undergoes significant metabolic transformation.
It can be hydrolyzed to form 6-keto-prostaglandin F1alpha
that is subsequently oxidized to 6-keto-prostaglandin E1
. Another pathway involves
PGI2 oxidation to 15-oxo-prostaglandin
I2  that is finally transformed by
PTGIS to 15-oxo-prostaglandin
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